Fenofibrate reduces lipoprotein associated phospholipase A2 mass and oxidative lipids in hypertriglyceridemic subjects with the metabolic syndrome

Rosenson, Robert S.

doi:10.1016/j.ahj.2007.12.012

Cited by 30Lipoproteins and Cardiovascular HealthLipid metabolism and disordersParaoxonase enzyme and polymorphisms

Fenofibrate reduces lipoprotein associated phospholipase A2 mass and oxidative lipids in hypertriglyceridemic subjects with the metabolic syndrome

Rosenson, Robert S.·2008·American Heart Journal

DOI 10.1016/j.ahj.2007.12.012

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Abstract

Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a macrophage-synthesized lipase that is primarily bound to small electronegative low-density lipoproteins (LDLs). Lipoprotein-associated phospholipase A2 oxidatively modifies LDL and generates the proinflammatory byproducts oxidized fatty acids (ox-FAs) and lysophosphatidylcholine. Fenofibrate reduces Lp-PLA2 mass; however, it remains unknown whether the anti-inflammatory effects of fenofibrate are related to changes in LDL subclasses. Methods This was a randomized, double-blind, controlled clinical trial designed to investigate the effects of 3-month treatment with fenofibrate (160 mg/d) on Lp-PLA2 mass, LDL subclasses, and ox-FAs among 55 hypertriglyceridemic (> or = 1.7 and < 6.78 mmol/L) subjects with the metabolic syndrome. Results Fenofibrate treatment lowered fasting Lp-PLA2 mass by 13.2% (-19.0 to -7.7) versus placebo (2.3% [-5.0 to 4.1], P = .0002) and total ox-FA by 15.5% (-34.2 to +1.4) versus an 11.5% increase with placebo (P = .0013). In age-, sex-, and treatment-adjusted models, changes in Lp-PLA2 mass were associated with reductions in chemical LDL cholesterol (r = 0.59, P < .01) and measured total LDL particles (LDL-Ps) (r = 0.64, P < .01) and small LDL-Ps (r = 0.57, P < .01). In models that included small LDL, effects of fenofibrate on Lp-PLA2 mass were attenuated (P = .125), but not in models that included LDL cholesterol (P < .0001) and LDL-Ps (P = .005). Changes in Lp-PLA2 mass were not significantly associated with changes in ox-FA or inflammatory markers. Conclusions Among hypertriglyceridemic subjects with the metabolic syndrome, fenofibrate therapy reduced Lp-PLA2 mass, and these changes were associated with fewer small LDL-Ps.

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Fenofibrate treatment typically reduces serum triglycerides by a mean change of −93.7 mg/dL (−39.3%), increases high density lipoprotein cholesterol by +5.5 mg/dL (+12.4%), and reduces low density lipoprotein cholesterol by −17.9 mg/dL (−12.3%).
“Typical changes in serum lipids as a result of FF treatment include clinically important mean reductions of serum triglycerides (TG) by a mean change of −93.7 mg/dL (−39.3%), increases of high density lipoprotein cholesterol (HDLC) by +5.5 mg/dL (+12.4%), and reductions in low density lipoprotein cholesterol (LDLC) by −17.9 mg/dL (−12.3%).”
From Fenofibrate and metabolic syndrome (2010) · cites this paper as [36]

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Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome
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Filippatos, T. D., Gazi, I. F., Liberopoulos, E. N., Athyros, V. G., Elisaf, M., Tselepis, A. D., & Kiortsis, D. N. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.07.010 · Cited by 84 · see citing works
Effect of Fibrates on Lipoprotein-associated Phospholipase A2 Mass and Activity: A Systematic Review and Meta-analysis of Controlled Clinical Trials
Simental‐Mendía, L. E., Simental-Mendía, M., Gamboa‐Gómez, C. I., Jamialahmadi, T., & Sahebkar, A. (2025) · Current Pharmaceutical Design · doi:10.2174/0113816128345231240925095400 · Cited by 1 · see citing works
Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects
Davidson, M. H., Bays, H. E., Stein, E., Maki, K. C., Shalwitz, R. A., & Doyle, R. (2006) · Clinical Cardiology · doi:10.1002/clc.4960290609 · Cited by 51 · see citing works

Authors: Rosenson, R. S.
Affiliations: University of Michigan (US)
Corresponding author: Rosenson, Robert S.
ORCID: Rosenson, Robert S.
Venue: American Heart Journal
Publisher: Elsevier BV
Published: 2008-03
Volume: 155
Issue: 3
Pages: 499.e9-499.e16
ISSN: 0002-8703 (ISSN-L)
DOI: 10.1016/j.ahj.2007.12.012
OpenAlex: W2065099374
Cited by: 30
References: 39
Citations by year: 2025: 1 · 2022: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 5
FWCI: 5.63
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: American Heart Journal (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Keywords: fenofibrate, lipoprotein-associated phospholipase A2, oxidized fatty acids, metabolic syndrome, hypertriglyceridemia, small dense LDL, LDL subclasses, LDL cholesterol, anti-inflammatory activity, lysophosphatidylcholine, LDL oxidation, statins, fibrates, triglycerides, inflammation, atherosclerosis risk
MeSH terms: Adult, Hypolipidemic Agents, Dose-Response Relationship, Drug, Double-Blind Method, Fatty Acids, Nonesterified, Female, Follow-Up Studies, Humans, Immunoenzyme Techniques, Lysophosphatidylcholines, Male, Middle Aged, Magnetic Resonance Spectroscopy, Fenofibrate, Hypertriglyceridemia, Treatment Outcome, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Metabolic Syndrome, 1-Alkyl-2-acetylglycerophosphocholine Esterase

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Fenofibrate reduces lipoprotein associated phospholipase A2 mass and oxidative lipids in hypertriglyceridemic subjects with the metabolic syndrome

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